The move comes following a disappointing 4-11-1 campaign and reported recent meetings with owner Jeffrey Lurie regarding Pederson's future with the organization.
"Coach Pederson and I had the opportunity to sit down and discuss what that collective vision would look like moving forward," Lurie said in a statement. "After taking some time to reflect on these conversations, I believe it is in both of our best interests to part ways."
Despite the Eagles' record, Pederson's offseason plans apparently had as much to do with his firing as Philadelphia's on-field performance. Lurie didn't agree with Pederson's proposed staff changes for 2021, which reportedly included a number of internal promotions, according to NFL Network's Ian Rapoport.
The Eagles become the seventh team with a head coaching vacancy. However, a number of attractive assistants have interviewed for jobs over the last two weeks.
One name Philly may consider for the position is former NFL passer and current Kansas City Chiefs quarterbacks coach Mike Kafka, per Rapoport.
The Eagles hired Pederson in 2016. He found success early on, leading them to their first Super Bowl in franchise history in the 2017 season. Philadelphia won four playoff games during the 52-year-old's tenure, a mark only topped by the New England Patriots in that span.
However, things took a major turn for Pederson in 2020. His roster was ravaged by injuries, Carson Wentz battled through the worst season of his career, and a rift between Pederson and Lurie had reportedly been growing since last offseason.
The sideline boss even threatened to quit in September after being pressured to fire former offensive coordinator Mike Groh, sources told Jeff McLane of the Philadelphia Inquirer.
Pederson's firing significantly increases the chances of Wentz staying in Philadelphia, a source told ESPN's Jeremy Fowler.
Now a free agent, Pederson could be a candidate for the New York Jets' coaching position given his strong relationship with general manager Joe Douglas, per ESPN's Adam Schefter.
Pederson wraps up his time in Philadelphia with a 42-37-1 record and a 4-2 postseason mark.
Responding to questions about the status of Howie Roseman, Lurie stood by his general manager.
"I have real confidence our football operations, led by Howie, can not only repeat the performance of 2016 to now but also create a dominant football team," Lurie said.